Last updated: 2026-09-13
In the CUHK team's 2017 study, 20,174 eligible, asymptomatic ethnically Chinese men underwent plasma EBV DNA screening; 1,112 were positive on the first test, 309 remained positive on the repeat test, and 34 were diagnosed in the first round. The positive predictive value is 34 ÷ 309 = 11.0% (corrected 95% confidence interval 7.8–15.2%). A positive result does not mean cancer, but it is also not a basis for deciding in advance that further investigation is "unnecessary": of the 9 people who declined further evaluation, 1 was diagnosed with advanced nasopharyngeal carcinoma 32 months after enrolment and died two months later. Of the cancers found in the first round, 71% were stage I or II; three-year progression-free survival was 97%, against 70% in a historical cohort. These are observational results from a non-randomised study, and the comparison alone cannot prove that screening lowers mortality. A negative result is not a guarantee either: the first-round paper records two initially negative participants diagnosed 4 and 22 months later. The Centre for Health Protection's leaflet of June 2025 states that there is insufficient evidence to recommend population-based nasopharyngeal cancer screening for asymptomatic people at average risk; for middle-aged people with a first-degree relative who has had nasopharyngeal cancer, the official advice is to seek a doctor's advice and make an informed decision about screening. The research figures, the limits of the test and the official recommendations are each set out below.
What is nasopharyngeal cancer? Why is it particularly common in Hong Kong and southern China?
Nasopharyngeal cancer is a malignant tumour of the nasopharynx, and it is the most common head and neck cancer in Hong Kong. The leaflet Nasopharyngeal Cancer Prevention and Screening — Cancer Prevention Series 8, published by the Centre for Health Protection of the Department of Health in June 2025, puts it this way:
Nasopharynx is a centrally located region in the head, between the posterior part of the nasal passage and the soft palate, and is connected to the pharynx underneath.
Nasopharyngeal Cancer is a malignant tumor in the nasopharynx. It is the most common head and neck cancer in Hong Kong.
The Centre for Health Protection's "Nasopharyngeal Cancer" health topic page (page self-dated 23 January 2026) describes the geographical distribution this way:
Nasopharyngeal cancer (NPC) is more common in the southern part of China than in Western countries. In 2023, NPC was the fifteenth commonest cancer in Hong Kong, accounting for 1.8% of all new cancer cases. In addition, NPC was the tenth commonest cancer in men.
How many cases are there? The Hong Kong Cancer Registry of the Hospital Authority records in Nasopharyngeal Cancer in 2023 (published by the Registry in Aug 2025): new nasopharyngeal cancer cases in 2023 of 549 in males and 151 in females, a male to female ratio of 3.6 to 1; a median age of 58 years for males and 56 for females; a lifetime risk before age 75 (0-74 years) of 1 in 100 for males and 1 in 460 for females. The age-standardised incidence rates printed on the same statistical sheet are 9.5 for males and 2.1 for females (per 100,000 population), with the note that these rates are calculated against the Segi (1960) World Standard Population, the Registry also stating that "Comparisons with these rates from other sources are valid only under the same standard population for calculations."
⚠️ For the same year and the same cancer, Hong Kong has two official age-standardised incidence rates. They are not in conflict; the standard populations differ. The 2023 age-standardised incidence rates printed on the Centre for Health Protection's page are 10.3 for males and 2.3 for females, and that page's own footnote states that they are compiled against the WHO 2001 world standard population. Whichever figure you use, you have to say which standard it uses; comparing rates requires the same standard population, and the case counts, years and populations covered have to correspond as well.
Why southern China? The Cancer Expert Working Group on Cancer Prevention and Screening's Recommendations on Prevention and Screening for Nasopharyngeal Cancer, For Health Professionals of June 2025 says:
The geographical distribution of NPC is extremely uneven across the globe, with over 70% of the new cases were reported in East and Southeast Asia, including Indonesia, Singapore, Vietnam and southern China. Some parts of southern China have particularly high incidence rates for NPC, such as Zhongshan (ASIR 25.0 per 100,000) and Zhuhai (24.0 per 100,000) of Guangdong Province.
That is, the document states that over 70% of new cases occur in East and Southeast Asia, including Indonesia, Singapore, Vietnam and southern China, and that Zhongshan (age-standardised incidence rate 25.0 per 100,000) and Zhuhai (24.0) in Guangdong Province are particularly high-incidence areas.
The same document also states that the age distribution of nasopharyngeal cancer differs from that of other common cancers: "Unlike most of the other common cancers, NPC is generally more common in middle-aged individuals. Locally, ASIR of NPC peaks at 60 to 65 years for male and at 50 to 55 years for female." That is, the document states that the local incidence rate peaks at 60 to 65 years in men and at 50 to 55 years in women. This local age distribution is not a risk score for any individual.
On risk factors, the Centre for Health Protection's leaflet (June 2025) lists five:
Risk factors of nasopharyngeal cancer include:
• First degree relatives (including parents, siblings, and children) of a nasopharyngeal cancer patient
• Prolonged and high intake of Chinese-style salted fish
• Epstein-Barr Virus (EBV) Infection
• Smoking
• Occupational exposure to wood dust and formaldehyde
Who most needs to know: middle-aged people with a first-degree relative who has had nasopharyngeal cancer, because the Government's recommendation of June 2025 addresses that group specifically — see the section below on the official recommendations.
How can a blood sample detect cancer? And why take a second sample four weeks later?
Because nasopharyngeal cancer cells release fragments of Epstein-Barr virus (EBV) DNA into the plasma; the test is not detecting viral particles. The introduction to the 2017 New England Journal of Medicine paper reads:
Nasopharyngeal carcinoma is prevalent in Southeast Asia. Among middle-aged men, the incidence of nasopharyngeal carcinoma in endemic areas is up to 35 cases per 100,000 persons, and risk factors include a family history of nasopharyngeal carcinoma, consumption of salted fish, and smoking. The pathogenesis of nasopharyngeal carcinoma is closely associated with Epstein–Barr virus (EBV), and circulating cancer-derived EBV DNA in plasma has been established as a tumor marker for nasopharyngeal carcinoma, with a sensitivity of 96% and a specificity of 93%. EBV DNA in plasma consists of short DNA fragments (primarily <181 bp) that are released by nasopharyngeal carcinoma cells, rather than being associated with viral particles.
That passage states that the development of nasopharyngeal carcinoma is closely associated with EBV; that the EBV DNA in plasma consists of short fragments (primarily shorter than 181 base pairs) released by nasopharyngeal carcinoma cells, rather than coming from viral particles.
Why the repeat test? The study uses a second blood sample to distinguish transient from persistent detection of EBV DNA. The team's second-round paper, published in NEJM Evidence in 2023, sets the three results out most clearly:
For individuals with a positive result on the baseline sample, another blood sample (follow-up sample) was collected 4 weeks later. Participants with undetectable plasma EBV DNA at baseline were defined as test negative. Participants with detectable plasma EBV DNA at baseline but undetectable 4 weeks later were defined as transiently positive. Participants with detectable plasma EBV DNA at baseline and 4 weeks later were defined as persistently positive and were referred for endoscopic examination and magnetic resonance imaging (MRI) of the nasopharynx. This two-stage testing arrangement aimed to differentiate patients with NPC from false-positive cases because patients with NPC would have persistently positive results, whereas individuals without this cancer tend to have transiently positive results.
So: anyone positive on the first test has a second blood sample taken four weeks later; being negative on the first test is "test negative", being positive on the first test but negative four weeks later is "transiently positive", and being positive on both is "persistently positive" — and only persistently positive participants were referred for nasopharyngeal endoscopy and magnetic resonance imaging. Table 1 of CUHK's English press release of 11 July 2023 carries a footnote with the same definition: "*Participants with detectable plasma EBV DNA at baseline that became undetectable four weeks later in the follow-up test".
⚠️ Four weeks is the designed arrangement; the interval actually achieved had a median of 34 days. The 2017 paper states: "The median interval between the first and the follow-up tests was 34 days (interquartile range, 30 to 40 days)."
The laboratory method and threshold the study used are also stated in the paper: 20 ml of venous blood from each person, real-time polymerase chain reaction targeting the BamHI-W fragment of the EBV genome, a lower limit of detection of 20 EBV genomes per millilitre of plasma, each sample tested in duplicate, and any amplification signal in either replicate counted as positive.
⚠️ The study had exclusion criteria. The paper states that recruitment was of "ethnically Chinese men who were 40 to 62 years of age", excluding people with a history of cancer, autoimmune disease, or ongoing systemic corticosteroid or immunosuppressive treatment, precisely in order to reduce false positives. This article does not apply the study's performance to women, to other age groups, or to the people excluded above — the reason being set out in the last section of this article, in the limitations the research team recorded themselves.
What are the figures at the four stages of the 20,000-person study? How far apart are a positive result and a diagnosis?
1,112, 309, 300 and 34 are, respectively, the numbers positive on the first test, persistently positive, undergoing endoscopy, and diagnosed, and the denominators differ. From the Results section of the 2017 paper:
The demographic characteristics of the 20,174 eligible participants are listed in Table 1. At enrollment, 1112 participants (5.5%) had detectable EBV DNA in plasma and received follow-up analysis of EBV DNA in plasma. The median interval between the first and the follow-up tests was 34 days (interquartile range, 30 to 40 days). Among the 309 participants who had persistently positive results, 300 underwent endoscopic examination and 275 also underwent MRI (Figure 1). Twelve participants declined to undergo MRI but underwent endoscopic examination. Nine participants declined to undergo any further evaluation. Thirteen participants had contraindications to MRI (Figure 1).
Doing the arithmetic (using the figures already quoted above): 1,112 − 309 = 803 people turned negative on the repeat test four weeks later and had no endoscopy or MRI; 300 − 34 = 266 people underwent further investigation and no nasopharyngeal carcinoma was found at the time. The paper also states the findings in those 266: 195 had a normal endoscopic examination and 71 had lymphoid tissue (which the paper describes as also common in healthy people), of whom 32 underwent biopsy, all negative for cancer.
| Stage | First round (recruited 2013–2016) | Second round (median 43 months after the first) | Source and that document's own date |
|---|---|---|---|
| Number screened | 20,174 (eligible participants) | 17,838; those re-invited excluded people who had already had nasopharyngeal cancer or another cancer (locally excised skin cancer excepted) | New England Journal of Medicine paper, 10 August 2017; NEJM Evidence paper, 27 June 2023 |
| Positive on the first blood test | 1,112 (5.5%) | 1,387 (this site's calculation of 1,387 ÷ 17,838 is about 7.78%) | New England Journal of Medicine paper, 10 August 2017; NEJM Evidence paper, 27 June 2023 |
| Still positive on the repeat test four weeks later (persistently positive) | 309 (1.5% of all participants; 27.8% of those positive on the first test) | 423 (2.37%) | New England Journal of Medicine paper, 10 August 2017; NEJM Evidence paper, 27 June 2023 |
| Underwent endoscopy / MRI | 300 underwent endoscopy, of whom 275 also underwent MRI | all 423 underwent endoscopy, 382 also underwent MRI | New England Journal of Medicine paper, 10 August 2017; NEJM Evidence paper, 27 June 2023 |
| Diagnosed with nasopharyngeal cancer | 34 (34 ÷ 300 = 11.3%; the study's PPV denominator is all 309 persistently positive participants) | 24 | New England Journal of Medicine paper, 10 August 2017; NEJM Evidence paper, 27 June 2023 |
| Positive predictive value (PPV) | 11.0% | this site's calculation of 24 ÷ 423 is about 5.7%; the CEWG document prints 5.6%, so the two differ | First round: 2017 paper; second-round numbers: Results of the 2023 paper; CEWG document of June 2025, paragraphs 15–16 |
These figures do not mean that someone with a positive result can skip the diagnostic investigations. The "Follow-up" part of the Results in the 2017 paper records that, among the 9 participants who declined further evaluation, a 55-year-old participant was diagnosed with advanced nasopharyngeal carcinoma 32 months later after a neck mass appeared, and died two months after that. The authors take the view that the tumour may already have been present at the time of screening and that earlier investigation might have brought diagnosis and treatment forward; that is the authors' interpretation of a single case, and cannot prove that this case would necessarily have had a better outcome under another arrangement. CUHK's 2017 English press release also records this case.
What is a "positive predictive value"? In the paper's own words:
Of the 20,174 participants who underwent screening, only 309 (1.5% of all participants and 27.8% of those who initially tested positive) had persistently detectable EBV DNA in plasma at baseline and at follow-up. Among these 309 participants, nasopharyngeal carcinoma was confirmed in 34 (11.0%). Low positive predictive values are typical for cancer screening studies performed in asymptomatic populations. For example, a recent Korean study that screened 45,855 asymptomatic participants for hepatocellular carcinoma with the use of alpha-fetoprotein analysis showed a positive predictive value of only 1.66%. The positive predictive value of 11% in this study is superior to the typical 3% value of existing blood-based tumor markers in a population-screening context. Furthermore, nasal endoscopic examination is safe, quick, and inexpensive as compared with tests to confirm most other solid tumors.
That is, the authors say that low positive predictive values are typical of screening studies in asymptomatic populations, and set against that a Korean liver cancer alpha-fetoprotein screening study (45,855 people, positive predictive value 1.66%), noting that this study's 11% is above the typical figure of about 3% for blood-based tumour markers.
A low positive predictive value represents a burden of investigation, but it is not a basis for deciding in advance that investigation is useless. The original text of paragraph 16 of the Expert Working Group's health professionals document of June 2025:
Findings of local studies indicated that the use of cell-free EBV-DNA as a biomarker for NPC screening would be a better screening tool in terms of its higher sensitivity, specificity and PPV as compared to that of seromarkers. Nevertheless, PPV remains low at 11% for initial screening and 5.6% for second-round screening. Over 90% of participants with positive screening result were actually false positive cases and had to receive unnecessary NP endoscopy and subsequent surveillance.
That is, the document takes the view that EBV DNA performs better than serological markers, but that the positive predictive value remains low, and uses "Over 90%" to describe the burden of false positives and subsequent investigation. That sentence is the document's summarising phrase, not the exact proportion among the 300 people investigated in the first round: 266 ÷ 300 = 88.7%; taking all 309 persistently positive participants as the denominator, those not diagnosed in the first round are 275 ÷ 309 = 89.0%, which still includes the 9 people who did not undergo investigation and who cannot all be treated as proven cancer-free. And no cancer found at the time of investigation does not mean the risk later is zero.
But "false positive" does not mean no meaning at all. Table 1 of CUHK's English press release of 11 July 2023 groups participants by their first-round test result and gives the numbers diagnosed with nasopharyngeal cancer in the second round and the relative risks: first-round negative 16,924 people, 17 diagnosed in the second round (0.100%, relative risk 1.0); first-round transiently positive 677 people, 3 diagnosed (0.443%, relative risk 4.4); first-round persistently positive 237 people, 4 diagnosed (1.688%, relative risk 16.8). ⚠️ The first-round negative group is the reference, with its relative risk set at 1.0; it is not itself an estimated comparison and has no confidence interval. The two comparisons made against it have wide intervals in the paper: transiently positive 4.4 (95% confidence interval 1.3 to 15.0), persistently positive 16.8 (95% confidence interval 5.7 to 49.6).
The relative risks above compare the study population that completed the second round of screening and had not been diagnosed in the first; the absolute proportions are about 0.1%, 0.4% and 1.7% respectively. They are not an individual's probability of developing cancer, nor can a personal repeat-testing interval be set from a relative risk multiple alone.
How reliable is the figure that 71% were stage I or II?
The value itself has never changed, but the precision with which it was published was corrected in March 2018 — the width of the 95% confidence interval went from 2.9 percentage points to 32.0 percentage points. The comparison sentence in the original 2017 paper:
Histologically proven undifferentiated nasopharyngeal carcinoma was confirmed in 34 (11%) of the 300 participants who underwent further assessment. Figure 2A shows the stage distribution in these participants as compared with all patients with nasopharyngeal carcinoma in Hong Kong as recorded in the 2013 Hong Kong Cancer Registry. A significantly higher proportion of these participants had stage I and II disease than those in a historical cohort (71% vs. 20%, P<0.001 by the chi-square test).
That is, all 34 were histologically proven undifferentiated nasopharyngeal carcinoma; the paper compares the stage distribution of this group with all nasopharyngeal carcinoma patients in Hong Kong as recorded in the 2013 Hong Kong Cancer Registry, giving a stage I and II proportion of 71% against 20%.
⚠️ The figure for the comparison group depends on which document you read. The body of the paper gives 20% and states for itself that the comparison is the 2013 record of the Hong Kong Cancer Registry; the table in CUHK's Chinese and English press releases of 10 August 2017 prints 22%, with the comparison group labelled "Historical Cohort in HK", with no year and no source printed. The Expert Working Group's health professionals document of June 2025 returns to the paper's 20%, writing it as "when compared to the population in Hong Kong in 2013 (20%)". This article handles them separately: 71% and 20% belong to the paper; 22% belongs to the press release. This article does not treat the press release's 22% as a figure of the study itself.
The correction itself, published in the New England Journal of Medicine on 7 March 2018, reads:
Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer Original Article, N Engl J Med 2017;377:513-522. An error occurred in the calculation of the confidence intervals (CIs) for measures of the diagnostic performance of the screening program. The calculation was based on the Wilson CI, with continuity correction derived from Newcombe et al. (Statistics in Medicine 1998;17:857-72), but an error in the computer script used for the calculation resulted in a 5% CI instead of a 95% CI. This error affected the CIs given in five rows in Table 2 (page 519). The 95% CI for “Sensitivity” should have been 83.4–99.9, rather than 95.5–98.7; for “Specificity,” 98.5–98.8, rather than 98.6–98.7; for “Positive predictive value,” 7.8–15.2, rather than 10.7–11.3; for “Negative predictive value,” 99.97–100.00, rather than 99.99–100.00; and for “Proportion of stage I/II disease in the 34 cases of nasopharyngeal carcinoma identified by screening,” 52.3–84.3, rather than 69.6–72.5. The article is correct at NEJM.org.
That is, the correction states that an error in the computer script used to calculate the confidence intervals produced a 5% interval rather than a 95% interval, affecting five rows of Table 2 in the original paper. The corrected 95% confidence intervals: sensitivity 83.4–99.9 (originally printed 95.5–98.7); specificity 98.5–98.8 (originally 98.6–98.7); positive predictive value 7.8–15.2 (originally 10.7–11.3); negative predictive value 99.97–100.00 (originally 99.99–100.00); and the proportion of stage I/II disease among the 34 screen-detected cases 52.3–84.3 (originally 69.6–72.5).
⚠️ In one sentence: 71% is still 71%, but its 95% confidence interval changed from 69.6–72.5 to 52.3–84.3, and the width of the interval from 2.9 percentage points to 32.0 percentage points. In the same way, the 95% confidence interval of the 11.0% positive predictive value changed from 10.7–11.3 to 7.8–15.2.
⚠️ Paragraph 14 of the Expert Working Group's health professionals document of June 2025 still prints the uncorrected intervals — "97.1% (95% CI 95.5%-98.7%)", "98.6% (95 CI 98.6%-98.7%)", "PPV was 11.0% (95% CI 10.7%-11.3%)" — while item 25 of the same document's reference list already lists that correction ("Erratum in: N Engl J Med. 2018 Mar 8;378(10):973. doi: 10.1056/NEJMx180004."). Where this article quotes intervals, it uses the corrected values throughout, and says that they are the corrected ones.
⚠️ This article does not subtract the study's 71% directly from the Cancer Registry's latest stage distribution. The Registry's Nasopharyngeal Cancer in 2023 prints, for 2023, stage I 5.7%, stage II 9.7%, stage III 38.4%, stage IV 36.0% and unstaged 10.1%, with the note that the classification follows the 8th edition of the AJCC cancer staging manual; the study's own cases were staged under the 7th edition. The staging editions differ, the unstaged 10.1% has not been allocated, and the two sets of proportions are not suitable for direct subtraction as a measure of screening effectiveness.
Does the Hong Kong Government recommend nasopharyngeal cancer screening?
For asymptomatic people at average risk, the Government's answer from 2016 to 2025 has been "insufficient evidence". From the Centre for Health Protection's English leaflet of June 2025:
Based on available international and local scientific evidence, the Government’s Cancer Expert Working Group on Cancer Prevention and Screening has made the following recommendations on nasopharyngeal cancer screening for local population:
Prevention
• All individuals are recommended to adopt a healthy lifestyle, including no smoking and healthy eating (including the avoidance of Chinese-style salted fish especially during early childhood).
For asymptomatic population at average risk
• There is insufficient evidence to recommend a population-based nasopharyngeal cancer (NPC) screening programme using Epstein-Barr virus (EBV) IgA serology or EBV DNA testing.
For asymptomatic persons at increased risk
• Persons at increased risk, such as middle-aged adults with first degree relative having NPC are advised to seek advice from doctors before making an informed decision about screening by EBV IgA serology or EBV DNA testing.
The same leaflet also states the purpose and the limits of screening:
The purpose of nasopharyngeal cancer screening is to detect nasopharyngeal cancer before it gives rise to symptoms, so that early treatment can be initiated. EBV IgA serology and EBV DNA testing are currently available screening tools. However, these tests are not 100% accurate and there is lack of evidence in their cost-effectiveness for screening population at average risk.
How have the official documents evolved? The Expert Working Group's health professionals document of March 2017 (recommendations made at the 26th meeting in June 2016) writes: "There is insufficient evidence to recommend a population-based nasopharyngeal cancer (NPC) screening programme using IgA against specific Epstein-Barr virus (EBV) viral antigens and EBV DNA test."; the nasopharyngeal cancer row of Annex B to Legislative Council paper CB(2)1433/18-19(01) (20 May 2019) writes: "There is insufficient evidence to recommend a population-based nasopharyngeal cancer ("NPC") screening programme for asymptomatic people using IgA against specific Epstein-Barr virus ("EBV") viral antigens and EBV DNA test."; and in the three documents of June 2025 — the Chinese leaflet, the English leaflet and the health professionals version — the answer in the average-risk column is the same.
⚠️ What actually changed in June 2025 is the "persons at increased risk" column. The 2016/2017 wording was "Family members of NPC patients may consider to seek advice from doctors with relevant expertise before making an informed decision about screening.", naming no test; the 2025 wording names EBV IgA serology and EBV DNA testing, and describes the group as "middle-aged adults with first degree relative having NPC". Naming the tests is the change; the answer for people at average risk is not.
Cost-effectiveness is one of the policy considerations. The health professionals document (June 2025) says:
In Hong Kong, no formal study on the cost-effectiveness of NPC screening has been conducted. Overseas cost-effectiveness study of NPC screening based on mathematical modeling suggested that once-lifetime, sex neutral EBV-based screening of middle-aged adults would be cost-effective in high-risk endemic regions of the world, using the incremental cost effectiveness ratios threshold of US$50 000/quality-adjusted life year to define highly cost-effective interventions in high-income countries.
That is, the document says that no formal cost-effectiveness study of nasopharyngeal cancer screening has been carried out in Hong Kong; an overseas study based on mathematical modelling suggests instead that, in the world's high-risk endemic regions, once-lifetime, sex-neutral EBV-based screening of middle-aged adults would be cost-effective. That is the Expert Working Group's summary of an overseas model; a model estimate does not mean an actual Hong Kong service has been shown to be cost-effective, and "no formal study" is that document's statement as at June 2025.
The concluding paragraph of the same document also says:
In summary, more justification from robust local cost-effectiveness data is required before recommending an NPC screening programme for the general population in Hong Kong.
That is, the document concludes that more robust local cost-effectiveness data are required before a nasopharyngeal cancer screening programme for the general population can be recommended.
What about symptoms? The leaflet covers them. The Centre for Health Protection's leaflet of June 2025 sets out:
Early stage of nasopharyngeal cancer usually has no symptoms and may not be easily noticed.
Common symptoms include:
• Stuffiness
• Nose bleeding or blood stained sputum
• Decreased hearing
• Tinnitus
• Recurrent ear infection
• Neck lump
• Unexplained headache
• Facial paralysis
• Double vision
• Hoarseness
• Difficulty in swallowing
You should see a doctor as soon as possible if you develop any of the above symptoms.
What limitations did the research team state themselves? Where can it be done in Hong Kong, and at what cost?
The study observed earlier diagnosis and better progression-free survival, but the interpretation has to take the study design with it. First, on effectiveness and bias:
The 3-year rate of progression-free survival among the participants in whom nasopharyngeal carcinoma was identified by screening was superior to that among those in the historical cohort (97% vs. 70%; hazard ratio, 0.10). In this study, the effect of length-time bias (which can occur when the lengths of intervals are analyzed by means of random selection or with respect to relatively nonprogressive cancers) is likely to be small because nasopharyngeal carcinoma is an aggressive cancer with frequent early progression and metastases. Even if a patient presents with carcinoma in situ at the time of diagnosis, the disease often progresses to invasive nasopharyngeal carcinoma in 40 to 48 months. The potential confounding effect of lead-time bias (in this case, the interval between early diagnosis with screening and later diagnosis with standard techniques) could be addressed only in randomized, controlled trials. However, because curative treatment for early-stage nasopharyngeal carcinoma is available, the increase in progression-free survival is unlikely to be driven by an earlier diagnosis only, but more likely by the timely administration of effective treatments.
That is: three-year progression-free survival among those diagnosed in the first round of screening was 97%, against 70% in the historical cohort (hazard ratio 0.10); "progression-free survival" is not the same as overall survival or nasopharyngeal cancer mortality. The authors take the view that the effect of length-time bias should be small, because nasopharyngeal carcinoma is an aggressive cancer; on the lead-time bias brought by earlier diagnosis, the authors state that it could be addressed only in randomised, controlled trials; and in the last sentence of the same paragraph the authors also state their view that the improvement in progression-free survival is unlikely to be driven by earlier diagnosis alone, but more likely by the timely administration of effective treatments.
The 2023 second-round paper reports separately: of the 24 cancers, 16 (67%) were stage I or II, with no stage IV; at a median follow-up of 33 months no recurrence had been seen, and three-year progression-free survival was estimated at 100%. The second round is a rescreening of the same study population, not a separate independent randomised trial. That paper's survival comparison uses a different historical cohort (78.8%), which should not be confused with the 70% of the first paper. These results support continued research, but the limitations — historical controls, bias from earlier diagnosis, and small numbers — mean they cannot directly prove a mortality benefit from population-wide screening.
Second, on people outside the study:
Although the current study focused only on men between the ages of 40 and 62 years, this screening protocol should also be applicable to women and persons in other age groups, in whom EBV DNA in plasma is also detected. However, a lower positive predictive value would be expected owing to the lower incidence of nasopharyngeal carcinoma among women and persons in other age groups.
That is, the authors say the study covered only men aged 40 to 62; they consider the protocol should also apply to women and other age groups, but expect a lower positive predictive value because the incidence in those groups is lower.
Third, on how long a single negative result stays "valid":
With a median follow-up of 22 months, the current study shows that the chance of the development of a nasopharyngeal carcinoma within 2 years after a negative screening is low. However, the most appropriate time interval for the screening can be addressed by a longer-term follow-up and rescreening of the cohort.
That is, the authors say that at a median follow-up of 22 months the chance of developing nasopharyngeal carcinoma within two years of a negative screen is low; but that the most appropriate screening interval can only be answered by longer follow-up and rescreening.
Low risk is not zero risk. In the negative group of the 2017 paper, two people were diagnosed with stage II nasopharyngeal carcinoma after 4 months and stage III after 22 months respectively. The sensitivity of 97.1% and the negative predictive value of 99.995% are calculated on cancers within one year of screening: among 19,865 people with a negative result, 1 was diagnosed within a year. That is not a lifetime guarantee. The 2023 paper separately records two first-round negative participants diagnosed at 28 and 39 months; the case timings in the two reports are presented separately, and are not combined here into a single cumulative risk estimate.
The interval to the second round of screening had a median of 43 months (interquartile range 41 to 45 months). Neither the 2017 nor the 2023 paper sets an optimal screening interval applicable to everyone; the study's actual arrangements are not a recommendation for a regular clinical check-up.
As for cost, the paper does its own arithmetic, but the research team states that it carried out no formal cost analysis. The 2017 paper gives the cost of each EBV DNA analysis, endoscopy and MRI as US$30, US$80 and US$1,000 respectively, and writes "to detect 1 case, 593 participants would need to be screened at a cost of $28,600". The 2023 second-round paper writes: "Although we did not conduct a formal cost analysis, we estimate that the cost to detect one NPC case is in the range of US$25,000 to US$40,000." That is, the authors say they did not conduct a formal cost analysis, and estimate the cost of detecting one nasopharyngeal cancer case at between US$25,000 and US$40,000.
Public sector arrangements and private list prices have to be understood separately. The 5 policy materials this article consulted — the CEWG health professionals versions of 2017 and 2025, the Centre for Health Protection's Chinese and English leaflets of 2025, and the 2019 Legislative Council paper on cancer prevention and screening — do not set out any Hospital Authority or Department of Health application procedure or itemised charge for providing plasma EBV DNA testing to asymptomatic people. That is a gap within this defined scope of material, and does not mean that public clinical services could not arrange the test.
Healthgene's EBeasy product page lists a qualitative EBV DNA test at HK$580 with a reservation deposit of HK$200, and lists a quantitative test at HK$1,500 in the related-products area of the same page. That is a single organisation's list price as published on 13 September 2026; the page does not give an effective date for the prices. 1 product page is not enough to represent Hong Kong market prices, a price range, or the total number of organisations offering the test; and a qualitative and a quantitative test cannot be treated as the same protocol as the study merely on the basis of their names. This is price information, not a recommendation of an organisation or of a test.
Common questions
- If my plasma EBV DNA is positive, does that mean I have nasopharyngeal cancer? No. Of the 309 persistently positive participants in the first round of the study, 34 were diagnosed, a PPV of 11.0% (corrected 95% confidence interval 7.8–15.2%); the proportion diagnosed among the 300 who underwent endoscopy was 11.3%. Not being diagnosed is not proof of being permanently cancer-free: of the 9 who declined further investigation, 1 was later diagnosed with advanced cancer and died.
- Does a negative result rule out nasopharyngeal cancer? No. In the 2017 paper two first-round negative participants were diagnosed after 4 and 22 months; the sensitivity of 97.1% is an estimate within a one-year observation window. The Centre for Health Protection's leaflet tells anyone who develops symptoms to see a doctor as soon as possible, irrespective of whether they have had a negative screening result.
- Is the 71% stage I or II figure trustworthy? The observed value has not changed, but the 2018 correction changed its 95% confidence interval from 69.6–72.5% to 52.3–84.3%. The paper's 2013 historical comparison is 20%; the table in CUHK's press release gives 22%, and the two sources should not be mixed.
- Does the Government recommend it for everyone? The Centre for Health Protection's leaflet of June 2025 states that the evidence is insufficient for population-wide screening of people at average risk; for middle-aged people with a first-degree relative who has had nasopharyngeal cancer, the official advice is to seek a doctor's advice and then make an informed decision.
- Has screening been shown to be cost-effective in Hong Kong? The CEWG document of June 2025 states that no formal local study had been conducted at that time, and takes the view that more robust local cost-effectiveness data are required before a programme for the general population can be recommended. The detection-cost estimates set out in the two CUHK papers are not a completed formal cost-effectiveness evaluation.
- How common is nasopharyngeal cancer in Hong Kong? The HKCaR's 2023 statistics give 549 male and 151 female cases, 700 in all; the Centre for Health Protection uses these to list nasopharyngeal cancer as the fifteenth most common cancer that year, accounting for 1.8% of all new cases.
Related article: 〈Your body check report says "abnormal" — what now?〉
What this article covers
This article compares a screening study in asymptomatic people, Hong Kong's official recommendations and the list price on one private product page; it does not provide an individual diagnosis, an individual screening interval or a treatment plan. The boundary of information on public sector testing arrangements is the 5 named policy documents above; private prices are limited to 1 named product page, from which no inference is drawn about the market as a whole.
The study's staging under the 7th edition of AJCC differs from the HKCaR's 8th edition staging for 2023, and there are also unstaged cases, so this article does not treat the difference between the two as a measure of screening benefit.
- This is the English edition. The Traditional Chinese edition is the authoritative version of this article. Quotations above are reproduced from the official English text published by the Government of the Hong Kong Special Administrative Region, or from the original English of the journal and university sources, not translated by this site. Where the Chinese edition prints a Chinese summary of an English quotation, the English edition keeps the accompanying explanation but drops the translation itself, because the quotation and the reader are now in the same language.
Sources
- Chan KCA et al., "Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer", N Engl J Med 2017;377:513-522 (10 August 2017), doi:10.1056/NEJMoa1701717: https://www.nejm.org/doi/full/10.1056/NEJMoa1701717 (Last updated: 2026-09-13)
- "Analysis of Plasma Epstein–Barr Virus DNA to Screen for Nasopharyngeal Cancer" (CORRECTION), N Engl J Med 2018;378:973 (7 March 2018), doi:10.1056/NEJMx180004: https://www.nejm.org/doi/full/10.1056/NEJMx180004 (Last updated: 2026-09-13)
- "Plasma Epstein–Barr Virus DNA and Risk of Future Nasopharyngeal Cancer", NEJM Evid 2023;2(7) (27 June 2023), doi:10.1056/EVIDoa2200309: https://evidence.nejm.org/doi/full/10.1056/EVIDoa2200309 (Last updated: 2026-09-13)
- 香港中文大學醫學院,〈中大完成二萬人「血漿DNA」鼻咽癌篩查研究 大幅推前癌症發現期數〉(10 August 2017): https://www.med.cuhk.edu.hk/tc/press-releases/cuhk-completes-a-20000-person-plasma-dna-screening-study-of-nasopharyngeal-cancer-and-finds-a-dramatic-shift-to-early-stage-cancers (Last updated: 2026-09-13)
- The Chinese University of Hong Kong, Faculty of Medicine, "CUHK Completes a 20,000-person Plasma DNA Screening Study of Nasopharyngeal Cancer, and Finds a Dramatic Shift to Early Stage Cancers" (10 August 2017): https://www.med.cuhk.edu.hk/press-releases/cuhk-completes-a-20000-person-plasma-dna-screening-study-of-nasopharyngeal-cancer-and-finds-a-dramatic-shift-to-early-stage-cancers (Last updated: 2026-09-13)
- 香港中文大學醫學院,〈中大研究證實「血漿DNA」篩查能偵測到早期沒有病徵的鼻咽癌 並反映日後患鼻咽癌風險〉(11 July 2023): https://www.med.cuhk.edu.hk/tc/press-releases/cuhk-study-concludes-that-plasma-ebv-dna-screening-can-detect-early-asymptomatic-nasopharyngeal-cancer-and-reflect-the-risk-of-future-cancer-development (Last updated: 2026-09-13)
- The Chinese University of Hong Kong, Faculty of Medicine, "CUHK study concludes that plasma EBV DNA screening can detect early asymptomatic nasopharyngeal cancer and reflect the risk of future cancer development" (11 July 2023): https://www.med.cuhk.edu.hk/press-releases/cuhk-study-concludes-that-plasma-ebv-dna-screening-can-detect-early-asymptomatic-nasopharyngeal-cancer-and-reflect-the-risk-of-future-cancer-development (Last updated: 2026-09-13)
- 衞生署衞生防護中心非傳染病處,〈鼻咽癌預防及篩查——預防癌症系列(八)〉(June 2025): https://www.chp.gov.hk/files/pdf/8_npc_prevention_and_screening_chi.pdf (Last updated: 2026-09-13)
- Non-communicable Disease Branch of Centre for Health Protection, Department of Health, "Nasopharyngeal Cancer Prevention and Screening — Cancer Prevention Series 8" (June 2025): https://www.chp.gov.hk/files/pdf/8_npc_prevention_and_screening_eng.pdf (Last updated: 2026-09-13)
- Cancer Expert Working Group on Cancer Prevention and Screening, "Recommendations on Prevention and Screening for Nasopharyngeal Cancer, For Health Professionals" (June 2025): https://www.chp.gov.hk/files/pdf/npc_hp_version_hp.pdf (Last updated: 2026-09-13)
- Cancer Expert Working Group on Cancer Prevention and Screening, "2016 Recommendations on Prevention and Screening for Nasopharyngeal Cancer, For Health Professionals" (March 2017): https://www.chp.gov.hk/files/pdf/8_npc_hp_version_hp.pdf (Last updated: 2026-09-13)
- Subcommittee on Issues Relating to the Support for Cancer Patients, Panel on Health Services, Legislative Council, "Cancer Prevention and Screening", LC Paper No. CB(2)1433/18-19(01) (20 May 2019): https://www.legco.gov.hk/yr18-19/english/panels/hs/hs_scp/papers/hs_scp20190520cb2-1433-1-e.pdf (Last updated: 2026-09-13)
- Hong Kong Cancer Registry, Hospital Authority, "Nasopharyngeal Cancer in 2023" (Aug 2025): https://www3.ha.org.hk/cancereg/pdf/factsheet/2023/npc_2023.pdf (Last updated: 2026-09-13)
- Centre for Health Protection, Department of Health, "Nasopharyngeal Cancer" (page self-dated 23 January 2026): https://www.chp.gov.hk/en/healthtopics/content/25/54.html (Last updated: 2026-09-13)
- Private sector product page, "EBeasy (Qualitative) DNA Test" (the page carries no self-printed date or price version): https://www.healthgene.com.hk/product/ebeasy-qualitative/?lang=en (Last updated: 2026-09-13)
Official recommendations and prices may be updated; the announcements of the relevant organisations govern. This article is health information, not medical advice, and cannot judge whether any individual should undergo any test. If you develop any of the symptoms listed in the Centre for Health Protection's leaflet, that leaflet says you should see a doctor as soon as possible; in an emergency, go at once to the nearest Accident and Emergency Department.
